The multivalency of cold-reactive IgM anti-lymphocyte autoantibodies, together with the local density of reactive antigens on the cell surface, may confer a capacity for a variety of immunoregulatory and non-specific physiological roles in the immune system and in SLE and other autoimmune diseases. Targets of interest in this regard include CD45, β2 microglobulin, and surface immunoglobulin. IgG anti-lymphocyte autoantibodies, while more difficult to study, also exhibit interesting specificities. However, whether any of the mechanisms by which anti-lymphocyte autoantibodies could alter cellular function actually obtain in vivo remains speculative. Essentially all of the data in this regard derive from experiments in which anti-lymphocyte autoantibody-containing SLE serum or plasma, or purified Ig fractions thereof, is combined with peripheral blood mononuclear cells in short-term culture in vitro. Thus, it is possible that anti-lymphocyte autoantibodies in SLE, rather than contributing to pathogenesis, reflect a physiological attempt by the immune system to restore homeostasis in the face of aggressive autoimmune stimulation.